DE102021112251B4 - opto-electronic chip - Google Patents

Abstract

.Opto-electronic chip for recording a sample during the visualization of temperature-dependent processes with a carrier layer, a thin-film light guide and a thin-film heating element, the thin-film light guide and the thin-film heating element being either on opposite sides of the carrier layer or on the same Side of the carrier layer are arranged, wherein the sample and / or particles contained therein can interact with an originating from a guided mode of the thin-film light guide evanescent field.

Description

The present invention relates to an opto-electronic chip for recording a sample when visualizing temperature-sensitive processes and an optical system with such a chip, in particular a microscope for total internal reflection microscopy (TIRM).

The U.S. 2006/0210232 A1 , the EP 0 642 052 A1 and the U.S. 2004/0202420 A1 disclose prior art opto-electronic chips.

TIR microscopy is preferably used to examine structures that are very close (between 0 and 200 nm for visible light) to a surface, for example a surface of a slide that is in contact with a sample, in particular an opto-electronic chip . These can be, for example, fluorescently labeled molecules or scattering centers in the membrane of a cell or close to it, individual DNA molecules bound to the surface, or other structures. In contrast to classic microscopy, TIR microscopy offers the advantage of better signal resolution. This is created by selectively illuminating the area of the cover glass close to the surface in classic TIR microscopy or specifically in the area close to the surface of the opto-electronic chip. This illumination is generated by a field whose intensity decreases exponentially from the surface, also known as an evanescent field. This generates a high contrast between the signal near the surface and the background scattered light.

Traditionally, TIR microscopy uses an objective with a very high numerical aperture to ensure that the light for optical excitation of the sample is totally reflected at an angle shallower than the critical angle at the interface between the coverslip and the sample. The illumination geometry, in particular the exponential decay of the evanescent field, is directly related to the angle at which the light exits the lens. However, the systems for adjusting this angle are very temperature sensitive and the field of view is limited to a few hundred µm ² . As soon as the temperature of the sample and thus often also the lens changes by just a few degrees Celsius, the sample illumination changes significantly.

However, since TIR microscopy is often used for When studying temperature-sensitive biological processes (e.g. to determine the binding affinity between a protein and an antibody or of living cells), it is essential for many applications to set the sample to a specific temperature in order to obtain usable data.

Against this background, it is an object of the present invention to mitigate or even completely eliminate the problems of the prior art. In particular, the present invention is based on the object of creating a device which eliminates the need for an objective with a very high numerical aperture and allows the sample to be set to a desired temperature reliably and quickly, as well as observing larger observation fields of up to a few mm ² allows

This object is achieved by an opto-electronic chip having the features of claim 1 and an optical system having the features of claim 13. Advantageous developments of the present invention are the subject matter of the dependent claims.

An opto-electronic chip according to the invention is used to hold a sample in the visualization of temperature-dependent processes and can therefore be viewed as a slide.

Such an opto-electronic chip has a carrier layer, a light guide (also referred to below as a waveguide), preferably a thin-film light guide, and a heating element, preferably a thin-film heating element, with the light guide and the heating element preferably being on opposite sides of the Carrier layer are arranged.

If the term thin-film light guide is used below, it is to be understood that this merely reflects a preferred embodiment and that other light guides are also encompassed by the invention. If the term thin-film heating element is used below, it is to be understood that this only reflects a preferred embodiment and that other heating elements are also encompassed by the invention.

The heating element and/or the light guide is/are preferably optically transparent.

In this case, optically transparent material is preferably more transmissive for light in the range visible to humans, with the transmission of the light through the optically transparent material preferably being at least 0.5, in particular at least 0.8. Optically opaque material is in this case preferably rather impermeable to light in the range visible to humans, with the Transmission of the light through the optically opaque material is preferably at most 0.49, in particular at most 0.3.

The light guide and/or the heating element can be arranged directly on a surface of the carrier layer or can be spaced apart from it by one or more intermediate layers.

In addition, the light guide and/or the heating element and/or the carrier layer can each be designed as a single layer or as a composite of two or more sub-layers.

The carrier layer preferably consists entirely or at least partially of an opaque or transparent material, preferably of Si or an SiO 2 -based glass or crystal.

The carrier layer thus consists, for example, of glass, in particular borosilicate glass, and is preferably designed to impart mechanical stability to the optoelectronic chip.

Furthermore, a further transparent layer can be located between the carrier layer and the thin-film waveguide, which has a lower refractive index than the carrier layer, preferably a refractive index between 1.2 and 1.5.

According to one embodiment of the invention, the carrier layer is made entirely or at least partially from a semiconductor material, preferably Si, and there is preferably also a transparent layer, in particular a separating layer, between the carrier layer and the light guide, preferably the thin-film light guide.

Furthermore, the thin-film heating element is preferably connected and/or equipped with a temperature sensor, preferably in the form of a thin-film temperature sensor, which preferably forms at least a partial area of a surface of the opto-electronic chip, which is designed to be directly in contact with a sample or to get in touch indirectly.

For example, as part of the temperature sensor, a sensor layer for detecting the temperature of the sample can be provided, which preferably has metal and/or consists of metal and which preferably at least partially covers an outer surface of the optoelectronic chip and is also preferably designed for this purpose to contact a sample.

The temperature is preferably measured using the temperature sensor at at least one location in the sample, preferably at a plurality of locations, in order to obtain a more reliable measured value.

A four-wire measurement is preferably used as part of the temperature sensor.

Furthermore, the opto-electronic chip preferably has a control unit in order to control and/or regulate the thin-film heating element on the basis of the measurement data relating to the sample temperature recorded by means of the temperature sensor.

Preferably, a thin film heating element used within the scope of the invention is or comprises a resistance heating element. For example, carbon nanotubes can be used as part of the heating element.

In order to ensure that particles and/or objects and/or molecules to be examined can be localized close to a surface of the opto-electronic chip and thus in the area of the evanescent waves, it has proven advantageous in practice if an outer surface of the opto-electronic chip, which is designed to come into contact with the sample, has at least partially or completely a surface modification and/or surface functionalization in order to remove molecules contained in the sample (or other particles and/or objects), in particular biological molecules, to bind.

A surface functionalization can include, for example, providing the surface with specific functional chemical groups, for example hydroxyl groups, in order to specifically bind a desired class of molecules to the surface.

Furthermore, the present invention relates to the use of an opto-electronic chip according to the invention for recording a sample in the visualization of temperature-dependent processes, a sample, preferably an at least partially liquid, solid or gel-like sample, being applied to the opto-electronic chip in such a way that the sample partially or completely covers the thin-film light guide and preferably also the sensor layer of the temperature sensor. A chip according to the invention can also be used with a microfluidic system.

For example, an inventive opto-electronic chip can be used to a temperature-sensitive process at an exact to observe the controlled temperature of the sample. An opto-electronic chip according to the invention can also be used to examine the temperature dependence of a process by observing the process at different, precisely controlled temperatures of the sample.

The sample used within the scope of the present invention preferably contains at least one or a plurality of particles and/or objects and/or molecules which are capable and/or designed to do so, with a guided mode (also referred to as mode) of the thin-film Light guide to interact. For example, the molecules are excited to fluoresce by the light guided or guided by the light guide, deflect this light and/or absorb the light.

A further aspect of the invention relates to an optical system, preferably a microscope, particularly preferably a TIR microscope, which is designed to be used with an optoelectronic chip according to the invention.

An optical system according to the invention preferably has at least one emitter, which sends light into the thin-film waveguide for optical excitation, and at least one detector, which detects light deflected and/or emerging from the sample normal to the plane of the thin-film light guide.

This setup physically separates the light paths used to excite the sample and detect the light, eliminating general stray light that occurs when the light is coupled into the waveguide or when the light is guided in the waveguide, and stray light due to local scattering of light through the sample and background light are reduced. This leads to an improved ratio between the desired detected signals from the sample compared to undesired signals caused by the measurement setup.

In order to guide light in a mode that is typical for the optical waveguide, coupling modules such as, for example, grating couplers, prism couplers and/or direct coupling mechanisms between two optical waveguides are preferably used. These coupling modules are used to introduce external light into the waveguide. More efficient coupling modules can increase the efficiency of the interaction between the emitter and the light guide.

The light guide directs the light of the excited guided mode over the opto-electronic chip and thus also through the volume of the sample.

The light guided by the light guide can be reflected back and/or coupled out. Coupling modules such as grating couplers, prism couplers and/or direct coupling mechanisms between two light guides are preferably also used for this purpose.

It is also conceivable that, by means of additional coupling modules, an optical mode of a different wavelength propagating simultaneously through the light guide, different optical modes of the same wavelength or a combination thereof are guided. An interaction of these within the waveguide and their detection can be used for highly sensitive measurements of the refractive index on the chip surface.

In an optical system according to the invention, the detector is preferably an array detector and/or the optical system is a microscope.

Furthermore, the invention relates to the use of an optoelectronic chip according to the invention and/or an optical system according to the invention for determining a phase transition of an (organic or an inorganic) particle contained in the sample or of a spatially extended material. This phase transition can include, for example, the change in a biological molecule, for example an enzyme, a protein or a deoxyribonucleic acid (DNA) or ribonucleic acid (RNA).

Another aspect of the invention relates to the use of an optoelectronic chip according to the invention and/or an optical system according to the invention in the context of high-throughput sequencing, preferably based on the analysis of individual molecules.

Yet another aspect of the invention relates to the use of an optoelectronic chip according to the invention and/or an optical system according to the invention for investigating the binding affinities between at least one protein and at least one antibody as a function of temperature. Furthermore, the invention relates to the use of an optoelectronic chip according to the invention and/or an optical system according to the invention for examining living cells under temperature-controlled conditions and their interactions with individual particles.

At this point it is pointed out that the terms "a" and "an" do not necessarily refer to exactly one of the elements, although this represents a possible embodiment, but can also refer to a plurality of elements to. Likewise, the use of the plural also includes the presence of the element in question in the singular and conversely the singular also includes several of the elements in question.

• 1 schematisch einen erfindungsgemäßen opto-elektronischen Chip;
• 2 schematisch ein erfindungsgemäßes opto-elektronisches System;
• 3 einen Querschnitt eines anderen erfindungsgemäßen opto-elektronischen Chips; und
• 4 eine Draufsicht des erfindungsgemäßen opto-elektronischen Chips aus 3.

Further advantages, features and effects of the present invention result from the following description of preferred exemplary embodiments with reference to the figures. This shows:

• 1 schematically an opto-electronic chip according to the invention;
• 2 schematically an opto-electronic system according to the invention;
• 3 a cross section of another opto-electronic chip according to the invention; and
• 4 a plan view of the opto-electronic chip according to the invention 3 .

1 shows an opto-electronic chip 1 according to the present invention. The chip 1 has a carrier layer 2 , in this embodiment made of a transparent silicon-based material, a thin-film light guide 3 and a thin-film heating element 4 . The thin-film light guide 3 and the thin-film heating element 4 are arranged on two opposite sides of the carrier layer 2. FIG.

A separating layer 5 made of a transparent material is arranged between the carrier layer 2 and the thin-layer light guide 3 .

A further separating layer 6 is arranged on the side of the light guide 3 facing away from the carrier layer 2 and is positioned between the light guide 3 and a metallic sensor layer 7 which is used to record the temperature of the sample 8 . In this representation, the sample 8 contains a particle 10 or another object, for example a molecule.

In this configuration, the sensor layer 7 is connected to a control unit (not shown), which controls and/or regulates the heating element 4 on the basis of the data recorded by means of the sensor layer 7 . The electronic circuit for controlling and/or regulating the heating element 4 is in 1 shown only stylized and denoted by the reference numeral 9.

The heating element 4 can be operated in a feedback mode, in which the value read out from the temperature sensor, in particular from the sensor layer 7, is used as a feedback parameter. The regulation preferably takes place electronically. There is also the possibility of using the heating element 4 unregulated or without feedback regulation.

2 shows an optical system in which a chip 1 according to the invention is used. The chip 1 is reproduced in a very simplified manner in this illustration; only the carrier layer 2 and the light guide 3 are shown.

Light is coupled into the light guide 3 by an emitter (not shown) in order to excite it. In the representation in 2 the light of the excited guided mode (also referred to as "guided mode") of the light guide 3 propagates from left to right through the light guide 3, as shown in 2 shown by the solid line arrows.

The particle 10, which is very close to the surface of the light guide 3, can interact with the light of the propagating guided mode of the light guide 3, for example by the particle absorbing the light or being excited by the light to fluoresce. For example, the light can be deflected, scattered and/or reflected by the particle 10, as is shown in 2 shown by the arrows shown in dashed lines.

Such light influenced and deflected by the particle 10 can be detected, for example, by means of detectors 11, e.g. imaging systems. In this case, the path of the light detected in this way preferably runs normal, i.e. at right angles, to the plane of the thin-film light guide 3 and thus also normal or at right angles to the propagation direction of the excited guided mode of the light guide 3.

The light path to excite the light guide 3 (in 2 from left to right) and the light path for detecting light from the sample 8 and particle 10 respectively (in 2 top and bottom) are thus spatially separated from one another in this embodiment and preferably run normally, or in other words orthogonally, to one another.

In other words, the light deflected by the sample at right angles to the plane of the light guide 3 is detected in a spatially resolved manner from above and/or from below through the carrier layer of the chip 1. The light deflected by the sample at right angles to the plane of the light guide 3 can for example be red-shifted or blue-shifted relative to the guided mode of the light guide or also be resonant to this.

According to the invention, the sample and/or particles contained therein interact or interact with one of the guided modes of the light guide resulting evanescent wave, whereby the light of the guided mode is scattered, for example, absorbed or re-emitted with a different wavelength.

In addition, the resonant light conducted in the light guide 3 in the guided mode can be detected by means of photodetectors 12 and/or the light scattered in the guided mode of the light guide 3 can be detected. The light scattered into the guided mode of the light guide 3 is, for example, red-shifted or blue-shifted relative to the guided mode of the light guide.

• Licht wird über ein Kopplungsmodul in die Wellenleitermode geschickt oder eingeleitet. Ein Anteil des Einkopplungslichts kann reflektiert werden, ein anderer Anteil des Lichts kann durch die Mode transmittiert werden. Das transmittierte Licht kann in einem zweiten Kopplungsbereich wieder gestreut werden.

A typical procedure for optical excitation and detection, as in the context of a system according to 2 is used is reproduced below:

• Light is launched or launched into the waveguide mode via a coupling module. A proportion of the in-coupling light can be reflected, another proportion of the light can be transmitted through the mode. The transmitted light can be scattered again in a second coupling area.

Both parts of the light can be detected via a photodetector and used, for example, as a feedback signal or control parameter for stabilizing the intensity of the light part guided in the waveguide. For such intensity stabilization, the light reflected in the coupling-in area and/or the light of the waveguide mode transmitted in the coupling-out area can be used as a feedback signal in order to stabilize or change the intensity of the light in the waveguide in a controlled manner. For this purpose, a chip according to the invention can have a correspondingly configured controller.

Light can be coupled into the waveguide via more than one coupling module. Alternatively or additionally, light with a different polarization, wavelength, direction of propagation, etc. can also be coupled in simultaneously or sequentially. Light scattered via the coupling areas can also be used to analyze the sample volume.

A particle 10 (e.g. a biomolecule) can interact with the guided mode via the evanescent light component (active sample area). The light scattered by the particle (fluorescence and/or direct scattered light) can be detected in a locally resolved manner via one or two optical systems or detectors 11, which are preferably located above or below the optoelectronic chip. Light scattered by the particle 10 can also couple into the waveguide mode and be scattered via the coupling modules and thus detected.

3 shows another embodiment of the invention. In particular shows 3 a cross section of an opto-electronic chip 1 with an exemplary arrangement of layers and layer thicknesses. The active region 14 is defined by a protective layer 12, which in this embodiment runs out adiabatic (in principle, non-adiabatic transitions are also conceivable). The adiabatic transfer of the protective layer 12 is denoted by the reference number 13 . Only the active area 14 of the chip 1 comes into contact with a sample volume.

The protective layer 12 has a lower refractive index than the waveguide 3, preferably the refractive index of the protective layer is in the range from 1.3 to 1.5 in the visible range.

The adiabatic transition 13 from the protective region or a region of the protective layer 12 that is remote from or at a distance from the active region 14 to the active region 14 enables a mode transition without generating scattered light and/or a loss of light output, regardless of a refractive index of the sample volume.

Furthermore, the protective layer 12 prevents the occurrence of contamination in the coupling-in area and scattered light through any optional container or channel for receiving a sample on or in the optoelectronic chip. At the in 3 shown arrangement, the sample can be easily included in the trough formed by the active region 14.

The heating element 4 can be arranged on a side of the chip 1 opposite the active area 14 . Alternatively or additionally, a heating element 4 can be present between the separating layer 5 and the carrier layer 2 . Several heating areas can also be provided for a chip.

The temperature sensor or at least its sensor layer 7 can be arranged between the separating layer 5 and the carrier layer 2 . In principle, the sensor or at least its sensor layer 7 can also be arranged at a different point on the chip 1, but here it must be ensured that the temperature sensor and/or a component thereof is not located in the evanescent field of the waveguide 3.

The temperature sensor or the sensor layer 7, the separating layer 5 and the protective layer 12 are optional. Typical layer thicknesses in the context of an opto-electronic according to the invention The layers used in chips are shown below: protective layer 12 (optional): 100-1000 nm, preferably 300-800 nm, waveguide layer 3: 50-1000 nm, preferably 75-250 nm separating layer 5 (optional): 100-1000 nm, preferably 100-800 nm, support layer 2: 150-1000 µm, preferably 170-500 µm, heating element 4: 5-100 nm, preferably 10-50 nm. The in 3 Chip 1 shown has a width (measurement from right to left in 3 ) from 5-30 mm.

4 FIG. 12 shows a plan view of the optoelectronic chip from FIG 3 . the inside 4 Chip 1 shown has a width (measurement from right to left in 4 ) of 5 - 30 mm and a length (measurement from top to bottom in 4 ) from 40-100mm. One or more coupling regions 15 enable light to be coupled into and out of the guided waveguide modes. in the in 4 In the embodiment shown, two coupling areas 15 are shown at opposite ends of the chip 1 .

The coupling regions 15 and the waveguide 3 are preferably covered by the protective layer 12 and the waveguide layer 3 is only exposed in the active region 14 and can come into direct contact with the sample volume. The waveguide layer 3 can be partially or completely chemically functionalized. The active area 14 preferably has an area of 0.01 mm ² - 25 mm ² and the total area of the optoelectronic chip 1 is preferably 25 mm ² - 2000 mm ² .

• Die vorliegende Erfindung ermöglicht die Betrachtung eines großen optischen Beobachtungsfelds. Insbesondere durch die Trennung von Anregungs- und Detektionspfad wird es technisch möglich, einen größeren Probenbereich bzw. aktiven Bereich optisch anzuregen. Konventionelle TIR-Systeme beleuchten Probenbereiche von typischerweise wenigen 10^-3 mm², wohingegen die vorliegende Erfindung die optische Anregung von Flächen bis in den Bereich von einigen mm² ermöglicht. Dies eröffnet neue Möglichkeiten, hochparalellisiert eine große Anzahl von Biomolekülen zu detektieren. Darüber hinaus ermöglicht es die vorliegende Erfindung, komplexere biologische Systeme wie Zellen bzw. Zellhaufen optisch anzuregen und zu beobachten.

The present invention offers significant technical advantages, in particular the following advantages:

• The present invention enables viewing of a large optical field of view. In particular, by separating the excitation and detection paths, it is technically possible to optically excite a larger sample area or active area. Conventional TIR systems illuminate sample areas of typically a few 10 ^-3 mm ² , whereas the present invention enables the optical excitation of surfaces in the range of a few mm ² . This opens up new possibilities to detect a large number of biomolecules in a highly parallelized manner. In addition, the present invention makes it possible to optically stimulate and observe more complex biological systems such as cells or cell clusters.

In addition, an optoelectronic chip according to the invention offers homogeneous illumination of the sample area or active area in comparison to conventional TIR systems.

The signal-to-background ratio is also improved with an optoelectronic chip according to the invention. In comparison to conventional TIR systems, such an optoelectronic chip offers a greatly reduced scattered light background, since the exciting light field is not guided through the detection optics.

Furthermore, the present invention offers the advantage that the depth of penetration of the evanescent field into the sample volume can be varied over a large range by skillfully selecting the waveguide layer parameters and the wavelength of the light. This penetration depth can vary from a few 10 nm to several 100 nm, depending on the layer and sample properties and the wavelength of the light.

In addition, due to the optical excitation via the waveguide mode, the use of lenses with a high numerical aperture is no longer necessary, since the required angle of incidence of the light is supported by the waveguide mode. Also, the use of immersion media is no longer necessary to achieve total internal reflection conditions, which greatly improves usability.

Furthermore, the temperature of the sample can be set very quickly by locally heating the sample volume using a chip according to the invention. According to the invention, heating rates of up to 100° C./s are possible. Since only small sample volumes are heated, the heat capacity is low and the environment alone allows the sample to cool down quickly to ambient temperature with (cooling) cooling rates of more than -20°C/s.
Conventional approaches to macroscopic temperature regulation involve various disadvantages, such as long equilibration times, thermal drifts, deteriorated optical imaging properties, etc., which are circumvented by the present invention.

In addition, the integration of a thin-film temperature sensor into the opto-electronic chip enables direct feedback control of the heating element. This ensures highly precise and dynamic temperature regulation of the sample volume.

The high sensitivity of the optoelectronic chip with regard to optical excitation and thermal changes also enables the calorimetric detection of phase transitions.

By integrating a highly sensitive excitation, a heating element and optionally a temperature sensor into the opto-electronic Chip, the overall system can also be greatly reduced in size and complexity.

Since the opto-electronic chip has no moving elements, mechanical wear or vibration of the entire system is avoided and the mechanical stability of the system is optimized.

The structure of the optoelectronic chip is still fundamentally compatible with microfluidic channels. In particular, the use of a protective layer with an adiabatic transition to the active sample area ensures the functionality of the excitation system independent of the refractive index of the sample volume if this is lower than the mode index of the waveguide, and / or of a potential sample container or channel, which is on or in the optoelectronic chip is located.

Claims (15)

.Opto-electronic chip for recording a sample during the visualization of temperature-dependent processes with a carrier layer, a thin-film light guide and a thin-film heating element, the thin-film light guide and the thin-film heating element being either on opposite sides of the carrier layer or on the same Side of the carrier layer are arranged, wherein the sample and / or particles contained therein can interact with an originating from a guided mode of the thin-film light guide evanescent field. opto-electronic chip claim 1 , characterized in that the carrier layer consists completely or at least partially of an opaque or transparent material, preferably of Si or a SiO2-based glass or crystal. opto-electronic chip claim 1 or 2 , characterized in that there is a further transparent layer between the carrier layer and the thin-film light guide, which has a lower refractive index than the carrier layer, preferably a refractive index between 1.2 and 1.5. opto-electronic chip claim 3 , characterized in that the further transparent layer consists of a polymer or an amorphous or crystalline material. Opto-electronic chip according to one of the preceding claims, characterized in that the thin-film heating element is equipped with a temperature sensor, preferably in the form of a thin-film temperature sensor, and preferably a control unit is also present to control the thin-film heating element on the basis to control and/or regulate the measurement data recorded by means of the temperature sensor. Optoelectronic chip according to one of the preceding claims, characterized in that the heating element is optically transparent and/or consists of an indium tin oxide compound. Opto-electronic chip according to one of the preceding claims, characterized in that the thin-film heating element is or comprises a resistance heating element. Optoelectronic chip according to one of the preceding claims, characterized in that a sensor layer is also provided, which preferably has metal and/or consists of metal and which preferably at least partially covers an outer surface of the optoelectronic chip and is furthermore preferably designed to to come into thermal contact with a sample. opto-electronic chip claim 8 , characterized in that temperature regulation takes place by means of a feedback system between the sensor layer and the heating element. Optoelectronic chip according to one of the preceding claims, characterized in that an outer surface of the optoelectronic chip, which is designed to come into contact with a sample, at least partially or completely has a surface modification and / or surface functionalization to contained in the sample To bind molecules, in particular biological molecules. Use of an opto-electronic chip according to one of the preceding claims for recording a sample in the visualization of temperature-sensitive processes, wherein a sample, preferably an at least partially liquid, solid or gel-like sample, is applied to the opto-electronic chip in such a way that the sample Thin-film light guide partially or completely surrounds. use after claim 11 , characterized in that the sample contains at least one or a plurality of particles capable and/or adapted to interact with a guided mode of the thin-film light guide. Optical system, preferably microscope, designed to be used with an opto-electronic chip according to one of the preceding claims, having at least one emitter or scatterer which emits light for optical excitation of the sample parallel to the plane of the thin-film light guide and with at least one detector which detects light deflected by the sample normal to the plane of the thin-film light guide. Optical system after Claim 13 , characterized in that the detector is an array detector and / or the optical system is a microscope. Use of an opto-electronic chip according to one of Claims 1 until 10 and/or an optical system Claim 13 or 14 for determining a melting point of an individual particle contained in the sample, preferably a biological molecule, for example an enzyme, a protein or a deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) or in the context of high-throughput sequencing based on the analysis of individual molecules or for Investigation of the binding affinities between at least one protein and at least one antibody as a function of temperature or to investigate living cells under temperature-controlled conditions.

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